Is normal hematopoiesis maintained solely by long-term multipotent stem cells?

Is normal hematopoiesis maintained solely by long-term multipotent stem cells?
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DOI:
10.1182/blood-2010-09-255679
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发表时间:
2011-04-28
期刊:
影响因子:
20.3
通讯作者:
Leboulch, Philippe
Leboulch, Philippe
中科院分区:
医学1区
文献类型:
--
作者:
Cavazzana-Calvo, Marina;Fischer, Alain;Leboulch, Philippe

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了解人类造血系统的等级组织具有重要的生物学意义和临床意义。在传统的模型中,造血完全由多能长期造血干细胞库维持,这种模型的有效性最近受到了几项小鼠研究的挑战。这些新的数据表明,存在一个由不同的LT-HSCs亚群组成的异质干细胞群体,其中包括偏向于谱系特异性分化计划的干细胞。本文在载体整合位点分析的基础上,对3个不同的基因治疗试验中采集的人LT-HSCs的谱系输出平衡模式和偏向模式进行了讨论。观察到的整合位点的分布倾向于支持修订后的模型的有效性。(血。2011年;117(17):-4424)
The understanding of the hierarchical organization of the human hematopoietic system is of major biologic and clinical significance. The validity of the conventional model in which hematopoiesis is solely maintained by a pool of multipotent long-term hematopoietic stem cells (LT-HSCs) has been recently challenged by several mouse studies. These new data point to the existence of a heterogeneous stem cell population that consists of distinct subsets of LT-HSCs, which include stem cells biased toward lineage-specific differentiation programs. This review attempts to discuss the balanced versus biased patterns of lineage output of human LT-HSCs gathered in 3 different gene therapy trials on the basis of vector integration site analysis by deep sequencing. The distribution of integration sites observed tends to support the validity of the revised model. (Blood. 2011; 117(17): 4420-4424)